Human herpesvirus 6 (HHV-6) is a new member of the herpesvirus group, first isolated in 1986 by Salahuddin et al (Science, 1986;234:596-601). Current data suggest that the virus is ubiquitous in human and that infection occurs in early childhood. Our own studies of HHV-6 began February 1988, in the new NIAID Twinbrook facility. The overall objective of our studies is to understand virus replication, and virus host-cell interactions. Our progress during the past few months can be summarized as follows: (i) Virus propagation: A significant amount of effort in the first few months has been devoted to the methodology for virus propagation. We are now able to obtain high titer virus stocks corresponding to 108-109 tissue culture infectious units per ml. (ii) Characterization of viral genome and cloning of viral DNA: We have obtained general cleavage patterns for 25 restriction enzymes. Hind III clones representing approximately 40% of genome were obtained thus far. (iii) Development of genetic markers to be used in functional mapping and vector engineering: Progress has been made in selection of variants with altered cytopathology. We have also defined virus sensitivity to phosphonoacetate and to acyclovir as potentially useful markers for DNA replication enzymes. (iv) Potential development of HHV-6 as a T cell vector. We have begun serial propagation of virus series containing defective virus genomes, so as to identify the cis-acting signals required for HHV- 6 DNA propagation. (v) Virus tropism: Preliminary results of studies done with purified T cells, B cells, and macrophages/monocytes have revealed a T cell trophism. (vi) Interaction with the host and the requirement for virus replication: Preliminary results have revealed that HHV-6 replication requires T cell activation and that this